甲氧苄氨嘧啶—PVP共沉淀物的研究

本工作用差示扫描量热法(DSC)研究甲氧苄氨嘧啶与PVP溶剂法制备的共沉淀物,表明已不存在甲氧苄氨嘧啶晶体。用x射线衍射法研究了1:12共沉淀物,证明无甲氧苄氨嘧啶的晶体衍射峰。经分光光度法测定结果,1:12共沉淀物比原药的溶解度大28.3倍。     

甲基苯丙胺抗体、疫苗以及检测试纸研究进展

苯丙胺类兴奋剂(amphetamine-type stimulants,ATS)是21世纪主要流行滥用的药物之一,目前社会上流行的"冰毒","摇头丸"等属于此类毒品,主要有甲基苯丙胺(methamphetamine,METH),亚甲基二氧基甲基苯丙胺(MDMA)等.在我国,此类毒品无论是在舞厅、迪吧或其它公共娱乐场所和地下色情场所等都很容易获得,导致滥用人群日益扩大[1],影响社会治安和社会稳定.虽然世界各国在药物滥用防治工作中投入了大量的人力、物力、财力,但收效甚微,对ATS依赖者目前治疗多采用强制戒毒、对症治疗和辅以心理治疗等方法,但治疗时间长,复吸率高[1-4],对于高危人群目前还没有一种有效的预防手段.检测ATS多用高效液相色谱(HPLC)、气相色谱-质谱联用(GC-MS)、薄层色谱(TLC)等[2]方法,其设备昂贵,难以开展现场检测,应用范围受限,并不适合于现场快速便捷检测,因而探索对ATS更有效的预防、治疗方法和更便捷的现场检测方法,极具现实意义.     

螺旋CT三期扫描对肝纤维化诊断价值研究

目的探讨螺旋CT三期扫描对肝纤维化的诊断价值。方法对66例经肝穿刺活检病理证实的慢性乙型肝炎肝纤维化患者组和42例正常对照组进行螺旋CT三期增强扫描。根据纤维化程度分期进行影像资料和相关指标的统计分析。结果肝左叶增大,肝表面形态及肝实质密度的改变,脾脏增大,门静脉增宽和侧枝循环的建立等影像学改变,随着肝纤维化严重程度的加重而有统计学差异。本研究显示57例肝纤维化患者螺旋CT三期扫描诊断肝纤维化52例,敏感性91.2%,特异性77.8%。各期肝纤维化分期准确28例,准确率49.1%;准确判断轻度纤维化(S1、S2)或重度纤维化(S3、S4)44例,准确率77.2%,诊断早期肝硬化16例,准确率84.2%。结论螺旋CT三期扫描能判断肝纤维化的程度,而且是动态观察肝纤维化的病程演进和临床随访的有效手段。     

急性冠状动脉综合征患者介入术前后血小板活化及血管内皮功能的变化

目的观察急性冠状动脉综合征患者介入治疗后血小板活化指标CD62p、CD63及糖蛋白Ⅱb/Ⅲa受体复合物及内皮功能的改变。方法60例急性冠状动脉综合征患者在冠状动脉介入术前和术后即刻以及次日采用流式细胞仪检测血小板活化指标CD62p、CD63及糖蛋白Ⅱb/Ⅲa受体复合物;双抗体夹心固相酶联免疫吸附试验测定血浆假血友病因子的表达水平;放射免疫测定法测定血浆内皮素1表达水平;酶法测定血浆一氧化氮的含量;彩色多谱勒超声诊断仪测量内皮依赖性血管舒张功能。选择健康体检者和稳定型心绞痛患者各30例作对照,观察急性冠状动脉综合征患者冠状动脉介入前后指标的变化并与对照组比较。结果与健康对照组和稳定型心绞痛组比,急性冠状动脉综合征组CD62p、CD63及糖蛋白Ⅱb/Ⅲa受体复合物明显增高(P<0.05或0.01);急性冠状动脉综合征患者介入术后即刻CD62p、CD63和糖蛋白Ⅱb/Ⅲa受体复合物与术前相比明显增高(P<0.01),但术后24h较术前无明显变化(P>0.05)。与健康对照组和稳定型心绞痛组比,急性冠状动脉综合征组假血友病因子、内皮素1的表达水平明显增高(P<0.01),内皮依赖性血管舒张功能和一氧化氮降低(P<0.05或<0.01);急性冠状动脉综合征患者介入术后即刻血浆假血友病因子和内皮素1水平升高(P<0.05或P<0.01),内皮依赖性血管舒张功能和一氧化氮水平降低(P<0.05),且介入术后24h假血友病因子水平也较术前升高(P<0.05),内皮依赖性血管舒张功能降低(P<0.05),但内皮素1和一氧化氮水平与术前差异无显著性(P>0.05)。结论血小板活化和内皮功能的损伤在急性冠状动脉综合征发生和发展过程中起重要的作用,冠状动脉介入术后血管内皮受到一定损伤,血小板有一定程度的激活。     

Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.     

Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

PR35THE INCIDENCE OF NON‐MELANOMA SKIN CANCER IN NEW ZEALAND

Background It is estimated that skin cancers cost $33 million per annum to the New Zealand healthcare system. Basal cell carcinoma and squamous cell carcinoma are the commonest types of non melanoma skin cancers (NMSCs). Anecdotal evidence indicates that there has been a doubling in the incidence of NMSCs in New Zealand over the last decade. Because of the high incidence mandatory reporting of NMSCs to the National Cancer Registry is not required. This lack of accurate data has led to poor health care policies and strategies including funding and workforce planning. Aims The aims of this study are to (1) present the latest statistics on NMSCs in New Zealand, including the incidence across different regions over the last decade, patient demographics, anatomic distribution of NMSCs, incidence and sites of metastasis, and disease‐specific survival; to (2) the histopathology of NMSCs, including surgical margins, histologic grade, and perineural, lymphatic, and vascular invasion; and (3) the relative role of different faculties treating NMSCs. Method This project has been approved by the multi‐centre ethics committee. A retrospective review was conducted from patients’ histology records from public and private pathology laboratories within defined catchment areas. Criterion for analysis is a confirmed diagnosis of NMSC treated surgically. A Microsoft Access database is created that will facilitate subsequent data retrieval and analysis. Results and Conclusion It is hoped that this up‐to‐date data will form the framework for the development of sound and sustainable healthcare policies of management of NMSCs including management strategies and workforce planning, and research direction on this common disease.